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To determine the effects of SARS-CoV-2 infection on cellular metabolism, we conducted an exhaustive survey of the cellular metabolic pathways modulated by SARS-CoV-2 infection and confirmed their importance for SARS-CoV-2 propagation by cataloging the effects of specific pathway inhibitors. This revealed that SARS-CoV-2 strongly inhibits mitochondrial oxidative phosphorylation (OXPHOS) resulting in increased mitochondrial reactive oxygen species (mROS) production. The elevated mROS stabilizes HIF-1α which redirects carbon molecules from mitochondrial oxidation through glycolysis and the pentose phosphate pathway (PPP) to provide substrates for viral biogenesis. mROS also induces the release of mitochondrial DNA (mtDNA) which activates innate immunity. The restructuring of cellular energy metabolism is mediated in part by SARS-CoV-2 Orf8 and Orf10 whose expression restructures nuclear DNA (nDNA) and mtDNA OXPHOS gene expression. These viral proteins likely alter the epigenome, either by directly altering histone modifications or by modulating mitochondrial metabolite substrates of epigenome modification enzymes, potentially silencing OXPHOS gene expression and contributing to long-COVID.

A monoclinic Y0.7Er0.3Fe2D4.2 compound exhibits unusual magnetic properties with different field induced magnetic transitions. The deuteride is ferrimagnetic at low temperature, and the Er and Fe sublattices present magnetic transitions at different temperatures. The Er moments are ordered below TEr = 55 K, whereas the Fe moments remain ferromagnetically coupled up to TM0 = 66 K. At TM0, the Fe moments display a sharp ferromagnetic–antiferromagnetic transition (FM–AFM) through itinerant electron metamagnetic behavior very sensitive to any volume change. Y0.7Er0.3Fe2D4.2 becomes paramagnetic above TN = 125 K. The pressure dependence of TEr and TM0 has been extracted from magnetic measurements under hydrostatic pressure up to 0.49 GPa. Both temperatures decrease linearly upon applied pressure with dTEr/dP = −126 and dTM0/dP = −140 K GPa−1 for a field of B = 0.03 T. Both magnetic Er and ferromagnetic Fe orders disappear at P = 0.44(4) GPa. However, under a larger applied field B = 5 T, dTM0/dP = −156 K GPa−1, whereas dTEr/dP = −134 K GPa−1 showing weaker sensitivity to pressure and magnetic field. At 2 K, the decrease of the saturation magnetization under pressure can be attributed to a reduction of the mean Er moment due to canting and/or a crystal field effect. Above TM0, the magnetization curves display metamagnetic behavior from an AFM to FM state, which is also very sensitive to the applied pressure. The transition field Btrans, which increases linearly upon heating, is shifted to a lower temperature upon applied pressure with ΔT = −17 K between 0 and 0.11 GPa. These results show strong decoupling of the Er and Fe magnetic sublattices vs temperature, applied field, and pressure. [ABSTRACT FROM AUTHOR]

HIV anti-retrovirals (ARVs) have vastly improved the life expectancy of people living with HIV (PLWH). However, toxic effects attributed to long-term ARV use also contribute to HIV-related co-morbidities such as heart disease, bone loss and HIV-associated neurocognitive disorders (HAND). Unfortunately, mouse models used to study the effects of ARVs on viral suppression, toxicity and HIV latency/tissue reservoirs have not been widely established. Here, we demonstrate an effective mouse model utilizing immune-compromised mice, reconstituted with infected human peripheral blood mononuclear cell (PBMCs). ARVs areincorporated into mouse chow and administered daily with combination ARV regimens includingAtripla (efavirenz, tenofovir disoproxil fumarate, and emtricitabine) and Triumeq (abacavir, dolutegravir and lamivudine). This model measures HIV-infected human cell trafficking, and ARV penetration throughout most relevant HIV organs and plasma, with a large amount of trafficking to the secondary lymphoid organs. Furthermore, the HIV viral load within each organ and the plasma was reduced in ARV treated vs. untreated control. Overall, we have demonstrated a mouse model that is relatively easy and affordable to establish and utilize to study ARVs’ effect on various tissues, including the co-morbid conditions associated with PLWH, such as HAND, and other toxic effects.

A versatile type of non-magnetic uniaxial pressure cell has been designed for magnetic measurements in SQUID magnetometer. An advanced technology of machining of miniature parts of the cell was used to make new type of an internal squeezer module, where a sample can be compressed by force up to 3 kN in direction perpendicular to external magnetic field. A correct operation of the cell was tested by study of magnetic behaviour of the Heusler off-stoichiometric Ni2MnSn alloy under uniaxial compression. An unexpected significant difference between reversible effects of uniaxial compression on magnetization of the austenite and martensite phases of the alloy is discussed. The uniaxial compression effects are compared with the effects of hydrostatic pressure on a coupling between magnetization and structural transformation of the alloy. [ABSTRACT FROM AUTHOR]